Evidence map›Paper›PMID 22965964›Full record

ArticleJournal of clinical oncology : official journal of the American Society of Clinical Oncology2012

Phase I study of a novel oral Janus kinase 2 inhibitor, SB1518, in patients with relapsed lymphoma: evidence of clinical and biologic activity in multiple lymphoma subtypes.

Anas Younes, Jorge Romaguera, Michelle Fanale, Peter McLaughlin, Frederick Hagemeister, Amanda Copeland, Sattva Neelapu, Larry Kwak, Jatin Shah, Silvana de Castro Faria and 5 more

Erratum issuedAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 74 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed, 1 pooled it
12.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

74 citing papers in PubMed, 1 synthesis or guideline pooled it, 139 citations in OpenAlex.

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  19. Novel agents and immune invasion in Hodgkin lymphoma.Hematology. American Society of Hematology. Education Program · 2019
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14 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 1 institution in 1 country.

Anas YounesDepartment of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. ayounes@mdanderson.org
Jorge Romaguera
Michelle Fanale
Peter McLaughlin
Frederick Hagemeister
Amanda Copeland
Sattva Neelapu
Larry Kwak
Jatin Shah
Silvana de Castro Faria
Stefan Hart
Jeanette Wood
Ramesh Jayaraman
Kantharaj Ethirajulu
Joy Zhu
Universidad San Jorge · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeThe Janus kinase 2/signal transducers and activators of transcription (JAK2/STAT) pathway plays an important role in the pathogenesis of hematologic malignancies. We conducted a phase I dose-finding and pharmacokinetic/pharmacodynamic study of SB1518, a potent JAK2 inhibitor, in patients with relapsed lymphoma. PATIENTS AND

methodsPatients with relapsed or refractory Hodgkin or non-Hodgkin lymphoma of any type except Burkitt's or CNS lymphoma were enrolled. Patient cohorts received escalating doses of SB1518 orally once daily for 28-day cycles. Response was evaluated after 8 weeks.

resultsThirty-four patients received doses of 100 to 600 mg/d. The maximum tolerated dose was not reached. Treatment was well tolerated, with mostly grade 1 and 2 toxicities. Gastrointestinal toxicities were the most common treatment-related events. Cytopenias were infrequent and modest. Pharmacologically active concentrations were achieved at all doses. Dose-related linear increases in area under the concentration-time curve were seen on day 1, with no significant accumulation on day 15. Mean terminal half-life was 1 to 4 days, and mean time to peak concentration ranged from 5 to 9 hours. SB1518 inhibited JAK2 signaling at 4 hours postdose at all levels. Increases in fms-like tyrosine kinase-3 (FLT-3) ligand, reflecting FLT-3 inhibition, were seen in most patients. There were three partial responses (≥300 mg/d) and 15 patients with stable disease (SD), with most responses lasting longer than 2 months. Seven of 13 SDs had tumor reductions of 4% to 46%.

conclusionSB1518 has encouraging activity in relapsed lymphoma, providing the first proof-of-principle of the potential therapeutic value of targeting the JAK/STAT pathway in lymphoma in the clinical setting.

Indexed as

Administration, OralAdultAgedAged, 80 and overBridged-Ring CompoundsCohort StudiesDose-Response Relationship, DrugFemaleHumansJanus Kinase 2LymphomaMaleMiddle AgedProtein Kinase InhibitorsPyrimidinesRecurrence11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaeneBridged-Ring CompoundsJanus Kinase 2Protein Kinase InhibitorsPyrimidines

Identifiers

PMID22965964
PMCPMC5950499
OpenAlexW2169404371

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.